E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ICD classification code: J45.0 and J 30.1 Rinoconjuntivitis +/- asma bronquial controlada |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039085 |
E.1.2 | Term | Rhinitis allergic |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001705 |
E.1.2 | Term | Allergic asthma |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this clinical trial is to prove the hypothesis that the recombinant allergen preparation rPhleum is suitable for an efficacious SCIT in grass pollen allergic patients and that the trial preparation is sufficient to suppress allergic symptoms caused by natural grass pollen exposure. The trial medication will be tested versus placebo in a total of 228 subjects. |
|
E.2.2 | Secondary objectives of the trial |
1. Change of AUC of RC-SMS after 1 and 3 treatment years. 2. Change of total Symptom-Medication-Score of rhinoconjunctivitis and asthma (SMS) after 1, 2 and 3 years. 3. Immunologic changes: specific IgG1 and IgG4 4. Improvement in specific conjunctival provocation. 5. Well days based on RC-SMS (no medication intake and maximum 2 score point). 6. Response status in terms of 40% improvement for the primary variable for an individual trial subject 7. Change of EQ-5D (before vs. after treatment)
Exploratory Assessments of additional basophile activation |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-1. Has the subject given informed consent according to local requirements before any trial-related activities? (A trial-related activity is any procedure that would not have been performed during the routine management of the subject and any other trial-related activity performed with trial specific diagnostics or with trial medication) 2. Is the subject a legally competent male or female outpatient? 3. Is the subject aged 12 - 65 year? 4. Does the subject suffer from IgE-mediated seasonal allergic rhinoconjunctivitis with or without asthma (controlled, acc. to GINA 2006) caused by grass pollen documented by o skin prick test wheal for grass pollen ? 5mm in diameter and o histamine (1,0% histaminedihydrochloride) wheal ? 3mm and o NaCl control reaction < 3mm and o EAST result (inhouse Allergopharma) ? 1.5kU/L to grass pollens and o proven clinical relevance of grass pollen allergy by positive conjunctival provocation testing with grass pollen allergens and o main discomfort in the months: - May, June, July and August of the year for Germany, Poland, the Netherlands, United Kingdom and France - April, May, June, July and August of the year for Spain o Does the subject with bronchial asthma at entry have a confirmed diagnosis of asthma and does his asthma has been classified as ?controlled? according to GINA guidelines (version 2006) with PEF or FEV1 at least 80% of predicted normal?
5. Has the subject been treated with anti-allergic medications for at least 2 years prior to enrolment? (Subjects with perennial and continuously treated asthma have to be excluded, see ?exclusion criteria? below.) 6. For female patients: Does the subject use effective contraception and does she have a negative pregnancy test result? (Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectibles, combined or oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. No pharmacological interactions are known for hormonal contraceptives and specific immunotherapeutic preparations.)
At the beginning of the treatment phase (November 2010): 7. Does the subject suffer from rhinoconjunctivitis symptoms documented in the subjects diary during the baseline season? 8. Does the subject have demonstrated a symptom-score of at least 4 per day during the week following the peak pollen count in the baseline season? |
|
E.4 | Principal exclusion criteria |
-unable to understand and comply with the requirements of the trial, as judged by the investigator -currently participating in any other trial or has the subject participated in any other trial within 30 days before inclusion in this trial -involved in the planning and conduct of the trial -an employee of Allergopharma Joachim Ganzer KG or of one of the trial sites -any relationship of dependence with the sponsor and/or with the investigator -previously enrolled or randomised to treatment in the present trial -mentally disabled -institutionalised due to an official or judicial order
For females with childbearing potential : -a positive pregnancy test before the baseline phase -use an unacceptable and unreliable contraceptive method during the trial, as judged by the investigator -pregnant or within the lactation period -seeking to become pregnant Immunotherapy criteria: -undergone previous specific immunotherapy with grass pollen allergens in any formulation -currently undergoing any sort of immunotherapy -ever undergone specific immunotherapy with unknown allergen or an unsuccessful immunotherapy -For allergens which interfere with the grass pollen season for all participating countries: Plantain, nettle, mugwort, alternaria alternata, cat epithelia, dog epithelia, Dermatophagoides farinae, Dermatophagoides pteronyssinus Additionally the following allergens will be tested in the following countries: Spain: olive tree UK: aspergillus ?skin prick test a wheal diameter of respective interfering allergen ? wheal diameter of grass pollen allergen or ?Sensitisation to respective interfering allergen as determined by serum EAST ? sensitisation to grass pollen -suffer from any clinically relevant perennial allergies (e.g. cat, mite) and clinical relevance can not be excluded
Disease and health status: -show a total IgE of > 2000kU/l -suffer from clinically relevant rhinoconjunctival or respiratory symptoms related to other reasons -PEF or FEV1 < 80% of predicted normal (ECSC) -uncontrolled or partly controlled asthma according to GINA guidelines (version 2006) -suffer from perennial and continuously treated asthma -suffer from rhinoconjunctival atopy symptoms for 20 years or longer -suffer from severe acute or chronic diseases (e.g. Diabetes mellitus type I, malignant neoplasia, chronic renal failure), severe inflammatory diseases -suffer from autoimmune diseases, immune-defects including immune-suppression, immune-complex-induced immunopathies -suffer from severe psychiatric and psychological disorders including impairment of cooperation -suffer from recurrent seizures? -suffer from irreversible secondary alterations of the reactive organ -any physiological and laboratory variables within/outside normal limits and as reported to be greater than Grade 1 changes according to the FDA Guidance for Industry an/or normal for population -treated with beta-blockers (locally and systemically) -any contraindication for use of adrenalin -completed or has an ongoing treatment with anti-IgE-antibody -completed or has an ongoing long-term treatment with tranquilizer or other psychoactive drugs -treated for allergy or asthma according to severity of symptoms with other than the following medication during the pollen season: Levocabastine nasal spray/eye drops, Loratadine/Cetirizine tablets, Salbutamol, inhaled corticosteroids up to a dose of 500µg/d BDP or equivalents, and exacerbation treatment with a short course of oral corticosteroids (Treatment with other medication must be stopped 2 weeks prior to start of the grass pollen season.) -using any prophylactic and any treatment with antiallergic medication in fixed (constant) dosage during the treatment phase of the trial |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this trial is the change of the area under the curve (AUC) of the Rhinoconjunctivitis Symptom-Medication-Score (RC-SMS) from the baseline season to the season after 2 years of treatment. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 64 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of open-label treatment phase |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |